Recent Developments in the Genetics of Attention-Deficit Hyperactivity Disorder

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Mental Health".

Deadline for manuscript submissions: closed (30 November 2021) | Viewed by 3792

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Guest Editor
Department of psychiatry, Psychotherapy and Psychosomatic Medicine, University Hospital of Würzburg, Würzburg, Germany
Interests: ADHD; bipolar disorder; perinatal mental disorders; hiPSC; genetics

Special Issue Information

Dear Colleagues,

Attention-deficit hyperactivity disorder is the most common neurodevelopmental disorder worldwide and persists into adulthood in about 60% of cases. Despite high heritability, with estimates of up to 80% based on twin and family studies, the genetic architecture of ADHD remains widely unknown. In addition, common and rare variants seem to be involved in ADHD genetic liability, though environmental and developmental factors also play a role. Disentangling the contribution of environment and genes is rather complex, however, recent studies with adequate designs that do just so are emerging. Furthermore, the increasing numbers of participants in the latest genome-wide association studies (GWAS) have revealed the first genome-wide loci associated with significant risk of ADHD development. Still, the molecular contribution of those risk gene variants to ADHD pathology have yet to be characterized, and new technologies like patient-derived neuronal cell models and brain organoids via human-induced pluripotent stem cells (hiPSC) might contribute to further elucidating the role of risk gene variants. Furthermore, emerging evidence points not only to a shared genetic risk between ADHD and other mental disorders but also somatic diseases, which seem to occur more frequently in ADHD. Therefore, given the increasing number of samples, new technologies, and sophisticated study designs, we will advance the goal of unravelling the mystery of the missing heritability of ADHD.

Prof. Dr. Sarah Kittel-Schneider
Guest Editor

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Keywords

  • attention deficit hyperactivity disorder
  • ADHD
  • ADD
  • genetics
  • risk gene variants
  • single-nucleotide polymorphisms
  • SNPs
  • copy number variants (CNV)
  • human-induced pluripotent stem cells (hiPSC)
  • brain organoids
  • somatic comorbidity

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Published Papers (1 paper)

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Research

20 pages, 3290 KiB  
Article
Energy Metabolism Disturbances in Cell Models of PARK2 CNV Carriers with ADHD
by Viola Stella Palladino, Andreas G. Chiocchetti, Lukas Frank, Denise Haslinger, Rhiannon McNeill, Franziska Radtke, Andreas Till, Simone Haupt, Oliver Brüstle, Katharina Günther, Frank Edenhofer, Per Hoffmann, Andreas Reif and Sarah Kittel-Schneider
J. Clin. Med. 2020, 9(12), 4092; https://doi.org/10.3390/jcm9124092 - 18 Dec 2020
Cited by 7 | Viewed by 3299
Abstract
The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were [...] Read more.
The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics. Full article
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